Topic 2 Energy Intermediary Metabolism

3 ways to consider energy metabolism

• whole body (short term)

• whole body (long term) → calorie counting

• cellular (chemistry of chemical reactions/”energy metabolism”)

  • can be aerobic and anaerobic

energy transferring molecules (define)

molecules that bind our energy and put them in bonds

• short-term fuel molecules

• long-term fuel molecules

ionic bonds (low energy)

covalent bonds (higher energy)

energy transferring molecules (list): used in oxidation/reduction reactions and in electrron and proton-transport pathways

• Nicotinamide Adenine Dinucleotide (NAD+/NADH + H+)

• Flavin Adenine Dinucleotide (FAD/FADH2)

• Coenzyme A (oxidized, reduced)

short-term fuel molecules

molecules tend to have covalently bound phosphate groups attached to a carrier molecule

• relatively unstable, not able to accumulate large amounts in cells

• adenine triphosphate (ATP), GTP, and UTP

• phosphagens (creatine phosphate, etc.): anything we slap the Pi on for energy

adenine triphosphate (ATP)

made of adenosine (adenine + ribose) and three phosphate groups

• the energy “currency” of the cells

• almost all metabolic activities requiring energy get energy by breaking this down to ADP

• also used for cell to cell signaling in the body + substrate for creating cAMP

• Delta G (change in Gibbs free energy): -7kcal energy/mol ATP (standard cond.)

• 1 kcal = 1 Cal = 1000 cal

• in cells, real conditions yield ~11 kcal/mol

creatine phosphate (CrP, CP, or PCr) aka phosphocreatine

• not stable; more stable than ATP, GTP, UTP

• Delta G (change in Gibbs free energy): -10.3 kcal/mol under standard conditions

• CrP regenerates ATP by substrate-level phosphorylation when total metabolism exceeds aerobic limit

phosphagens

physiologically produced organic molecules that store energy in phosphate bonds, ATP/CrP are the main phosphagens used in the human body

long-term fuel molecules

C-H bonds NOT phosphate bonds

• carbohydrates exist as monosaccharides, disaccharides and polysaccharides

• glucose → glycogen (polysaccharide)

• glucose is the principle monosaccharide used as fuel; ~4.2 kcal/g

• the body stores ~24 hrs worth of glycogen in liver and skeletal muscle

fats (triglycerides)

• long-term fuel molecules

• one glycerol molecule, three fatty acids (14-18 C long and ALWAYS an even # of C)

• fat provides ~9.4kcal/g

• most fat is stored in ADIPOSE (fat) cells, the body has no limit to how much fat can be stored

excess free amino acids (fuels) → long-term fuel molecules

• proteins are not typically synthesized for the purpose of “fuel storage” in the human body

• proteins can be degraded for fuel providing ~4.2-4.3 kcal/g

• specific proteins are made on an as needed basis by cells in order to accomplish some function

preference of fuels (calories)

• most calories from carbohydrates (glucose when fed)

• some calories from fats

• fewest calories from protein turnover and amino acids

under starvation conditions: body resorts to long-term fuel molecules (in this order)

• glycogen

• fats

• proteins

metabolism

all reactions of the body; what your cells are doing OR how much energy you’re using to do it

anabolism (anabolic)

building reactions (smaller pieces put together)

catabolism (catabolic)

breakdown reactions (bigger things taken apart to smaller pieces)

pathways

sets of chemical reactions that begin with a specific set of reactants and sequentially lead to a specific products

energy metabolism aka respiration

the catabolic pathways used to generate ATP

anaerobic respiration

doesn’t use oxygen

e.g. glycolysis is a catabolic pathway that is anaerobic

aerobic respiration

uses oxygen

e.g. krebs cycle and electron transport chain (aka oxidative phosphorylation) are two catabolic pathways that are aerobic

• though aerboic respiration is aerobic it begins with glycolysis

aerobic metabolism (examples)

• krebs cycle

• electron transport

glycolysis (with glycogenolysis)

what happens to pyruvate in glycolysis?

depends on whether oxygen is available

• pyruvate enters the mitochondria

• per pyruvate

  • makes 0 ATP

  • uses 2 NAD+ (acts as coenzymes)

  • makes 2 NADH+H+

enzymes

proteins that act as catalysts in chemical reactions

have ACTIVE SITES to bind to their substrates

most are highly specific

coenzymes

shuttle electrons/protons from fuel reactions to oxidative phosphorylation (electron transport) for ATP synthesis

(vitamin derivatives)

• low specificity

• organic (not proteins)

• catalysts

used in oxidation-reduction (REDOX) reactions

vitamin

organic molecule we need for life that we cannot make or synthesize

cofactors (minerals)

catalysts that help enzymes work

oxidize

removes e- or H

reduce

adds e- or H

krebs cycle

Acetyl CoA oxidized to CO2 and hydrogen ions, with accompanying electrons. Hydrogen ions and electrons are transferred to the ETC by the coenzymes NAD and FAD. one GTP is produced by substrate-level phosphorylation; each GTP can convert one ADP to ATP.

• requires a lot of oxidized coenzymes

• doesn’t use O2, synchronized with electron transport

oxidative phosphorylation (e- transport)

• occurs in mitochondria

• recycles 3 ATP per NADH+H+

• recycles 2 ATP per FADH2

• oxidizes the original coenzymes

  • NADH+H+ → NAD+

  • FADH → FAD+

• reduces oxygen to create water

All the ATP made per glucose

glycolysis = 2 NADH+H+

pyruvate→acetyl CoA (x2) = 2 NADH+H+

K.C. (x2) = 6 NADH+H+ and 2FADH2

• 2 NADH+H+ X 3 ATP/NADH+H+ = 6 ATP

• 2 NADH+H+ X 3 ATP/NADH+H+ = 6 ATP

• 6 NADH+H+ X 3 ATP/NADH+H+ = 18 ATP

• 2 FADH2 X 2 ATP/NADH+H+ = 4 ATP

Total ATP produced by oxid. phosphorylation = 34 ATP

• plus 2 ATP by substrate level phosphorylation in glycolysis

• plus 2 ATP (as GTP) by substrate level phosphorylation in krebs cycle

= 38 ATP per glucose by aerobic metabolism

anaerobic metabolism (accelerated glycolysis)

• never runs out of coenzyme (runs as fast as it wants to)

• can run as fast as it wants to

aerobic metabolism of other fuels

proteins: deamination of amino acids

fats: beta oxidation of fatty acids

lipolysis (process)

fats are hydrolyzed to glycerol and three fatty acids

β-oxidation

fatty acids degraded to many Acetyl CoA

β-oxidation of fatty acids

fats as fuel

proteolysis

proteins are hydrolyzed to amino acids

deaminated

all amino acids must go through this process to form keto acids (released amino groups → ammonia/converted to urea)

5 keto acids produced by amino acids that can be directly used in the glycolytic and KC pathways

• pyruvate

• alpha-ketoglutarate

• succinate (succinyl-CoA)

• fumarate

• oxaloacetate

most amino acids…

create keto acids that don’t directly fit into glycolysis or krebs cycle. these must be converted further or used in TRANSAMINATION reactions (to create one of the five keto acids)

proteins as fuel: transamination

intermediary metabolism

metabolism of a common pool of short chain (~2-4, can go up to 6 carbon) organic molecules that can be used to produce carbohydrates, proteins, or lipids

anabolism (pathway)

“building” pathways

catabolism (pathway)

“degrading” pathways

glycogenesis

anabolism of glycogen

gluconeogenesis (the -neo distinguishes creation vs. release)

anabolism of glucose

protein anabolism

anabolism of protein

lipogenesis OR lipid anabolism

anabolism of triglyceride

glycogenolysis

catabolism of glycogen, gives glucose

glycolysis

catabolism of glucose, gives pyruvate

proteolysis

protein catabolism, gives amino acids

lipolysis

catabolism of triglyceride, gives glycerol + 3 fatty acids

fat to glycogen (Study diagram)

protein to glycogen (Study image)